Medical quality assurance by Dr. Albrecht Nonnenmacher, MD at March 16, 2016

Phenylketonuria, more commonly known as PKU, is a rare disorder in which the body lacks an enzyme necessary to break down an amino acid found in proteins. The amino acid, called phenylalanine, can build up to dangerous levels leading to serious health problems and intellectual disabilities. Individuals with PKU must follow a diet limiting phenylalanine for the rest of their lives.


Definition & Facts

PKU is relatively rare in the United States. Approximately one in 10,000 to one in 15,000 newborns are diagnosed with the condition each year. In the United States, newborns are screened for PKU shortly after birth. If they are positive, they are immediately started on the appropriate PKU meal plan.

If untreated, PKU can cause severe intellectual disabilities, neurological problems, delayed development, as well as behavioral problems and psychological pain. PKU is an inherited genetic disorder. Those most at risk for inheriting PKU are individuals with two parents who have the PKU gene. The incidence of PKU varies among different ethnic groups and is least common among African-Americans.

Symptoms & Complaints

Most newborns do not develop symptoms of PKU until a couple of months after birth. Symptoms vary in severity and typically include:

  • Abnormally small head, also known as microcephaly.
  • Blue eyes and fair skin due to the fact that phenylalanine cannot form melanin, which is the pigment responsible for hair and skin tone.
  • Intellectual disabilities.
  • Developmental delays.
  • Frequent eczema.
  • Hyperactivity and other behavioral, emotional, and social problems.
  • Neurological problems, including seizures.
  • Weak bones.
  • Skin, breath, and urine have a musty odor due to the buildup of phenylalanine.
  • Mental disorders.

The most severe form of the condition is known as classic PKU. In this form of PKU, the activity of the enzyme, phenylalanine hydroxylase that breaks down phenylalanine is absent or severely reduced.

A less severe form, called variant PKU has a slightly lower risk of brain damage. In this version of the condition, the enzyme maintains some of its activity, which keeps phenylalanine levels from rising as high as with classic PKU. The majority of patients with either form require treatment with a special low-phenylalanine diet.


Phenylketonuria is caused by a genetic mutation in the PAH gene. This is the gene that contains the instructions for production of phenylalanine hydroxylase, which is the enzyme that converts the amino acid phenylalanine in the body to other compounds. Without this enzyme, phenylalanine can rise to dangerous levels whenever the individual eats high protein foods, such as meat or eggs.

For a child to inherit a defective PAH gene, both parents must have the defective gene. It is possible for the gene to be recessive in the parents. This means that neither parent has the disease, but both are considered carriers. This is the most common way in which PKU is passed from parent to child. If only one parent has the genetic mutation, the child will not have PKU but may be a carrier.

Diagnosis & Tests

Hospitals in the United States started routinely screening newborns for PKU in the 1960s, and it is now required in all 50 states. The test involves using a small needle or lancet to obtain a blood sample from the baby’s heel. The test is typically performed one to two days following birth. It is important that the test is performed after the baby has ingested protein to ensure accurate results. Mothers who don’t deliver their baby in the hospital should arrange for a PKU test with their doctor as soon as possible after birth.

If the preliminary test indicates PKU, the doctor may order additional blood tests and urine tests or genetic testing to confirm the diagnosis. If a parent has PKU or a family history of the condition, the doctor may order tests prior to pregnancy or birth. It is vital that women who have PKU follow their low-phenylalanine diet very carefully during pregnancy.

High levels of phenylalanine can pass from mother to baby leading to birth defects. If older children or adults start to develop symptoms of PKU, the doctor will likely order blood tests to check for the presence of the phenylalanine hydroxylase enzyme.

Treatment & Therapy

It is possible to relieve PKU symptoms and prevent complications with medications and a special diet. The PKU diet limits foods containing phenylalanine. Babies with PKU must avoid breast milk and are typically placed on a special formula called Lofenalac®. High protein foods excluded on the PKU diet include:

  • Beef
  • Pork
  • Chicken
  • Fish
  • Milk
  • Nuts
  • Beans
  • Cheese
  • Eggs

Individuals with PKU must consume a special PKU formula to ensure they are getting an adequate amount of protein. The formula contains all of the essential amino acids except phenylalanine. Some health food stores are now offering PKU-friendly foods. The PKU meal plan varies with the needs of the person and can change throughout life.

Individuals with PKU should work closely with a dietician or doctor to ensure they maintain healthy phenylalanine levels while still getting a balance of other nutrients. They will also have to keep a detailed record of all foods consumed during the day to keep phenylalanine levels in check.

The drug sapropterin was recently approved by the Food and Drug Administration to treat PKU. The drug is used in combination with the PKU meal plan and is most effective in those affected by a mild case of PKU.

Prevention & Prophylaxis

Since PKU is an inherited, genetic condition, there is no way it can be prevented. Individuals with PKU or a family history of the condition can undergo enzyme assay testing prior to having children to determine the potential risk of passing the condition along to their offspring.

Women with PKU can limit the likelihood of birth defects in their baby by following their diet carefully and working closely with their OB/GYN. All parents should have their children tested for PKU as soon as possible after birth. Children born with PKU can lead healthy, happy lives as long as they are started on the PKU diet as soon as possible after birth.